Topic 6 part 2 Flashcards
How is PFK regulated?
allosteric regulation (muscle)
inhibited by high ATP
stimulated by high AMP
hormonal regulation (liver)
stimulated by insulin
inhibited by glucagon
Where are the other sites of regulation?
Hexokinase regulated by allosteric inhibition from Glucose 6 phosphate
metabolic regulation-
high NADH causes product inhibition of step 6
inhibits glycolysis
hormonal activation-
PFK and pyruvate kinase
increase due to high insulin low glucagon ratio
How is PFK-1 phosphoregulated?
allosterically activated by- ATP:AMP ratio fructose 2,6 bisphosphate dephosphorylation of protein phosphatase 1 from insulin inhibited by - PEP, Citrate, hydrogen ions protein kinase A from glucagon
How is pyruvate kinase phosphoregulated?
activated by dephosphorylation of protein phosphatase 1 from insulin
inhibited by protein kinase A from glucagon
How is hexokinase regulated?
metabolically
inhibition at step 6 from high NADH
inhibition at step 4 PFK in response to high energy signals
prevents metabolism of F1,6 BP, backs up glycolytic intermediates, this increases the conc of G-6-P
G-6-P is a negative regulator of hexokinase
Where is the committing step in glycolysis?
step 3
phosphofructokinase 1
What is pyruvate dehydrogenase?
in mitochondria
large multi enzyme complex
different enzyme activities require various cofactors
b vitamins provide these factors so reaction is sensitive to vitamin B1 deficiency
reaction is irreversible, so is a key regulatory step
pyruvate cannot be formed by acetyl CoA
PDH deficiency leads to lactic acidosis
irreversible loss of carbon dioxide
Describe the main points of the TCA cycle
single pathway mitochondrial acetyl converted to 2 x carbon dioxide by carbon bonds broken oxidative (requires NAD+) some energy produced produces precursors for biosynthesis does not function in absence of oxygen intermediates act catalytically
Where has all the energy gone so far?
high energy electrons in NADH and FADH2 transferred to oxygen with the release of large amounts of energy, this energy is used to drive ATP synthesis
What do we use reducing power for?
electron transport-
release energy in steps, electrons on NADH and FADH2 transferred through a series of carrier molecules to oxygen
oxidative phosphorylation-
free energy release used to drive ATP synthesis
Describe the overall structure of a mitochondrion
outer mitochondrial membrane
intermembrane space
inner mitochondrial membrane
mitochondrial matrix
How are electrons transported in the mitochondrion?
through a series of carrier molecules to oxygen with release of energy
about 30% of energy used to move hydrogen ions across the membrane as a lot of energy is released as heat
the hydrogen ion gradient across the inner mitochondrial membrane is the proton motive force
How is ATP synthesis driven?
return of protons is favoured energetically by the electrochemical potential
protons can only return across the membrane via ATP synthase and this drives ATP synthesis
So, what is the process of oxidative phosphorylation?
electron transport coupled to ATP synthesis
electrons are transferred from NADH and FADH2 to molecular oxygen
energy release used to generate a proton gradient (pmf)
energy from the dissipation of the pmf is coupled to the synthesis of ATP from ADP
the greater the pmf the more ATP synthesised
How is oxidative phosphorylation regulated?
when ATP is high no substrate for ATP synthase
so inward flow of hydrogen ions stop
conc of H in intermitochondrial space increases
prevents further H pumping so stops electron transport
reverses with low ATP
Describe inhibition of oxidative phosphorylation
inhibitors block electron transport, prevents acceptance of electrons by oxygen
Describe uncoupling of oxidative phosphorylation
increase the permeability of mitochondrial inner membrane to protons
dissipate the proton gradient, thereby reducing the pmf
no drive for ATP synthesis
Describe brown adipose tissue
contains thermogenin a naturally occurring uncoupling protein
in response to cold, noradrenaline activates
- lipase which release fatty acids from triacylglycerol
- fatty acid oxidation, electron transport
- fatty acids activate thermogenin (UCP1)
- UCP1 transports H back into mitochondria
electron transport uncouple from ATP synthesis
energy of pmf is released as extra heat
How does oxidative phosphorylation differ to substrate level phosphorylation?
substrate level
requires soluble enzymes
energy coupling occurs directly through formation of high energy of hydrolysis bond
can occur to a limited extent in absence of O2
minor process for ATP synthesis in cells requiring large amounts of energy
oxidative
requires membrane associated complexes
energy coupling occurs indirectly through generation and utilisation of a proton gradient
can’t occur without O2
major process for ATP synthesis in cells requiring large amounts of energy
